Objective To investigate the anesthetic effectiveness of esketamine versus alfentanil combined with propofol in photodynamic therapy for port ⁃wine stains in pediatric patients. Methods 80 pediatric patients with port⁃wine stains who had received hemoporfin⁃mediated photodynamic were selected and randomly divided into two groups，sufentanil combined with propofol group（group S，n = 40）and esketamine combined with propofol group（group A，n = 40）. Anesthesia was induced and maintained with propofol in both groups. Group S was administered sufentanil 0.2 μ/kg before photodynamic therapy. In group A，esketamine 0.5 mg/kg was used before photodynamic therapy. The dosage of anesthetic drugs during treatment was recorded in both groups. Adverse events related to respiratory and circulatory system and the occurrence and degree of physical movement during photody⁃ namic therapy were noted. Anesthesia recovery time，pain scores and adverse effects during recovery period were also recorded. Results During photodynamic therapy，the incidences of hypotension，bradycardia，upper airway obstruction and hypoxemia were significantly lower in group A than in group S（P < 0.05）. There were no signifi⁃ cant differences between the two groups in the overall dose of propofol，incidence of body movement，recovery time，pain score and adverse events in the recovery period（P > 0.05）. Conclusions Esketamine combined with propofol can be safely and effectively used in hemoporfin⁃mediated photodynamic therapy for port⁃wine stains in pediatric patients，with little impact on breathing and circulation，and mild anesthesia⁃related adverse reactions.